Human CD200 protein is a type 1a transmembrane glycoprotein that is normally expressed on thymocytes (e.g., T cells and B cells), neurons, and endothelial cells. Through engagement with its cognate receptor, CD200R, CD200 protein transduces an immunoregulatory signal that can suppress T-cell-mediated immune responses. CD200 knockout animal studies as well as experiments using antagonist anti-CD200 antibodies and recombinant CD200-Fc fusion proteins have demonstrated that CD200 protein functions as an immunosuppressive agent in autoimmune disorder and during transplantation. (See, e.g., Hoek et al. (2000) Science 290:1768-1771 and Gorczynski et al. (1999) J Immunol 163:1654-1660). The interaction between CD200 and CD200R results in altered cytokine profiles and promotes a TH2 T cell response (humoral immune response) over a TH1 response (cellular immune response). See, e.g., Kretz-Rommel (2007) J Immunol 178:5595-5605.
The human immune system employs a variety of immunosurveillance mechanisms, which can identify malignant cells within a host organism and kill the cells before a cancer develops. See, e.g., Geertsen et al. (1999) Int J Mol Med 3(1):49-57; Kerebijn et al. (1999) Crit. Rev Oncol Hematol 31(1):31-53; and Pardoll (2003) Annu Rev Immunol 21:807-39. However, cancer cells are known to evade detection by the immune system. One potential mechanism by which cancer cells escape immunosurveillance is expression or overexpression of CD200 protein. In fact, CD200 protein has been shown to be expressed or overexpressed on a variety of human cancer cells including, e.g., B cell chronic lymphocytic leukemia cells, prostate cancer cells, breast cancer cells, colon cancer cells, and brain cancer cells. See, e.g., Kawasaki et al. (2007) Biochem Biophys Res Commun 364(4):778-782; Kretz-Rommel et al. (2007), supra; and Siva et al. (2008) Cancer Immunol Immunother 57(7):987-96.
Molecular biomarkers are often used in early drug development studies to determine, for example, whether a drug is biologically active in a patient—that the drug produced a measurable biological effect in the patient to which the drug is administered. For example, biomarkers can be useful during phase I studies to establish dosing schedules for future phase II studies and in general to help determine clinically-meaningful and optimized dosing schedules for treating patients suffering from disease. Biomarkers can also be useful for identifying the occurrence of potential side-effects or other non-therapeutic effects in a human treated with a drug to thereby determine a safety profile for the drug.